# Multi-Scale Modeling of Vascular Signaling Units

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $545,332

## Abstract

Project Summary
The function of arteries is to deliver oxygen and nutrients necessary to sustain the function and survival of every
cell in the body. Arterial diameter, a key determinant of blood flow, is finely tuned by the contractile state of the
smooth muscle cells lining the walls of these vessels. To date, however, models of myogenic control of arterial
smooth muscle tone have largely been based on data from male myocytes. Yet, recent data from our team
suggest that sex-specific features that determine the operation of arterial myocytes are attributable to differences
in the spatial organization of signaling complexes formed by the PKC-anchoring protein AKAP150 and CaV1.2
channels, and the manner in which they regulate smooth muscle contractility. Our findings challenge the general
applicability of a model for electrical and pharmacological control of the myogenic response based on data from
male myocytes and support the view that myogenic responses are differentially regulated in male and female
arteries. In this project, we implement a multi-scale systems approach that includes super-resolution imaging,
electrophysiology, and computational approaches to rigorously investigate the mechanisms controlling blood
flow through the male and female pial-parenchymal circulatory unit under physiological and pathological
conditions. Specific aim 1 is to establish the fundamental sex-specific mechanisms controlling Ca2+ influx via
CaV1.2 channels in vascular smooth muscle. Specific aim 2 is to determine the impact of the physical
organization of type 1 AngII receptors (AngIIR1), AKAP150, PKCα, and CaV1.2 channels on myogenic tone in
male and female arterial smooth muscle. Finally, in specific aim 3 we will investigate whether changes in the
number and molecular organization of CaV1.2 and AngIIR1/AKAP150/PKCα signaling units differentially alter
Ca2+ influx, arterial wall [Ca2+]i, and myogenic tone in male and female smooth muscle during the development
of hypertension. This work will lead to the first model of vascular smooth muscle function that incorporates sex-
specific variations in protein organization, electrical activity, and Ca2+ signaling during health and disease, which
could inform the development of rational strategies for the treatment of hypertension in male and female.

## Key facts

- **NIH application ID:** 10146477
- **Project number:** 5R01HL152681-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** COLLEEN E CLANCY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,332
- **Award type:** 5
- **Project period:** 2020-04-16 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146477

## Citation

> US National Institutes of Health, RePORTER application 10146477, Multi-Scale Modeling of Vascular Signaling Units (5R01HL152681-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146477. Licensed CC0.

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